Keio University Study Identifies Gut Epithelium as the Primary Site for Priming Pathogenic T Cells in Multiple Sclerosis

Researchers at Keio University find that intestinal epithelial cells prime the pathogenic T cells that cause brain inflammation in multiple sclerosis.

By: AXL Media

Published: Mar 28, 2026, 10:46 AM EDT

Source: Information for this report was sourced from Keio University Global Research Institute

The Intestinal Genesis of Autoimmune Neuroinflammation

Multiple sclerosis has traditionally been viewed as a primary disorder of the central nervous system, but new evidence suggests the disease may actually be "primed" in the human gut. A research team led by Dr. Shohei Suzuki and Dr. Tomohisa Sujino at Keio University has identified a specific cellular mechanism that links intestinal immunity to brain inflammation. According to the study, the body’s failure to distinguish between self and non-self proteins begins in the small intestine, where a unique interaction between the gut lining and immune cells generates the pathogenic triggers responsible for the destruction of myelin.

Uncovering MHC II Expression in the Gut Lining

The researchers discovered that intestinal epithelial cells, which typically serve as a simple barrier, undergo a significant functional shift in patients with multiple sclerosis. These cells begin to upregulate major histocompatibility complex class II (MHC II), a protein pathway normally reserved for specialized immune cells to "present" antigens to T cells. By performing single-cell RNA sequencing on intestinal biopsies, the team found that this abnormal antigen presentation occurs specifically in the ileum. This biological error essentially teaches CD4+ T cells to become aggressive, transforming them into pro-inflammatory Th17 cells that are programmed to attack the body's own tissues.

Tracking Pathogenic Cell Migration to the Spine

To confirm that these gut-activated cells are the same ones causing damage in the brain and spinal cord, the scientists utilized a sophisticated transgenic mouse model known as Kaede. This model allows researchers to "color-code" cells in the intestine using violet light and track their movement throughout the body. The study demonstrated that Th17 cells induced in the intestinal lining do not remain local, but instead migrate through the systemic circulation to the spinal cord. Once they reach the central nervous system, these gut-derived cells drive the chronic neuroinflammation that leads to the debilitating symptoms associated with multiple sclerosis.